Method of improving the appearance of aging skin

ABSTRACT

A stable skin care composition for improving the appearance of aging skin is disclosed. The stable skin care composition that includes an effective amount of artichoke leaf extract and carob fruit extract that, in combination, can provide a synergistic increase in the up-regulation of key epidermal-associated genes related to skin aging, and thereby provide an improvement in the appearance of aging skin. The stable skin care composition is substantially free of complexing agents and includes sunscreen agents to help photostablize the composition.

FIELD

The present invention relates to a stable skin care composition forimproving the appearance of aging skin, especially fine lines andwrinkles, using a synergistic combination of artichoke leaf extract andcarob fruit extract. The combination of artichoke leaf extract and carobfruit extract provides a synergistic increase in the upregulation of keygenes related to skin aging.

BACKGROUND

The epidermis, the outermost layer of the skin, comprises a cellularcontinuum of four layers: the stratum corneum, the granular layer, thespinous layer, and the basal layer. Each cellular layer in the epidermisrepresents various stages along a process in which basal epidermalkeratinocytes undergo a continuous cycle of proliferation,differentiation, and apoptosis, moving upward from the basal layer tofinally yield corneocytes. These corneocytes form the cornified layerknown as the stratum corneum.

Basal keratinocytes reside at the lower portion of the epidermis. Thesemitotically active cells undergo a proliferative cycle to generatedaughter cells that are physically dislocated upward into the spinousand granular layers and undergo the process of differentiation intocorneocytes. On passing through the spinous and granular layers, thecells undergo morphological changes that render them flatter instructure as they lose their cellular viability, undergo alternatekeratin expression profiles, and transform into cellular remnants. Onaverage, a younger-aged epidermis turns over in about one month,shedding the older cells and replacing them with newer ones, but thisprocess can increase to over forty days in older skin.

The stratum corneum's corneocytes remain connected to one other viaproteins and lipids, creating a protective barrier between the organismand its outside environment. This tightly regulated epidermalpermeability barrier functions as a physical and selective barrieragainst chemical and biological insults. Important functions of thisbarrier include attenuation of the penetration of free radicals andprevention of penetration of harmful radiation, including UV radiation,into deeper layers. The stratum corneum also acts as a permeabilitybarrier and functions to prevent loss of body moisture to the outsideenvironment. Dysfunction of this barrier can lead to chronic skinconditions, diseases, and in extreme cases can even threaten theviability of the organism.

Skin aging is a multifactorial process driven by both intrinsic(chronological aging) and extrinsic (environmental) factors, includingultraviolet (UV) exposure, environmental toxins, pollutants, andsmoking. It is well known in the art that the ability of the stratumcorneum to cyclically generate new layers of skin diminishes with age sothat the stratum corneum turnover rate is substantially reduced in agedskin, with the cornified layer becoming gradually thinner. This resultsin a reduction in the functioning capacity of the barrier so thatharmful stimuli penetrate the stratum corneum more easily, leading toUV-damage, for example, of the underlying dermal layers, degradation ofcollagen and elastin, and eventually manifests in appearance aswrinkling and skin atrophy. Thinning of the stratum corneum by the sumof intrinsic and extrinsic aging factors increases the visibleappearance of fine lines and wrinkles. Further, the barrier suffers froman age-related increase in permeability to free radicals and a reductionin the amount of lipid in the intercellular matrix, decreasing barriercapacity to diffuse toxins from deeper layers. Recovery capacity of thebarrier to environmental insult is also substantially reduced with age.

Thus, the skin's epidermal barrier function is key to the skin's abilityto regenerate and protect itself from the appearance of aging signs suchas fine lines and wrinkles. Accordingly, it would be desirable toprovide compositions and methods of treatment that can improve theskin's epidermal functioning and thus also improve the appearance ofaging skin.

SUMMARY

Disclosed herein are methods of improving the appearance of aging skin.In some embodiments, the method comprises applying an effective amountof artichoke leaf extract and carob fruit extract to an area of agingskin for a period of time sufficient to improve the appearance of theaging skin. In some embodiments, the area of aging skin may be agingfacial skin. In particular embodiments, improving the appearance ofaging skin comprises improving the appearance of aging skin texture suchas wrinkles, fine lines, coarse deep lines, crevices, bumps; preventingloss of skin elasticity, for example, due to loss, damage and/orinactivation of functional skin elastin, resulting in such conditions aselastosis, sagging, loss of skin recoil from deformation; andcombinations thereof.

In response to the problems identified in the background, the presentinvention may take other forms. Further forms of the present inventionwill be appreciated in the detailed description that follows.

DETAILED DESCRIPTION

All percentages and ratios used herein are by weight of the totalcomposition and all measurements made are at 25° C., unless otherwisedesignated. All numeric ranges are inclusive of narrower ranges;delineated upper and lower range limits are interchangeable to createfurther ranges not explicitly delineated.

The compositions of the present invention can comprise, consistessentially of, or consist of, the essential components as well asoptional ingredients described herein. As used herein, “consistingessentially of” means that the composition or component may includeadditional ingredients, but only if the additional ingredients do notmaterially alter the basic and novel characteristics of the claimedcompositions or methods. As used in the description and the appendedclaims, the singular forms “a,” “an,” and “the” are intended to includethe plural forms as well, unless the context clearly indicatesotherwise.

“Apply” or “application,” when referring to a composition, means toapply or spread the composition onto a human skin surface such as theepidermis.

“Dermatologically acceptable” means that a composition or componentsdescribed are suitable for use in contact with human skin tissue withoutundue toxicity, incompatibility, instability, allergic response, and thelike.

“Effective amount” means an amount of a compound or compositionsufficient to significantly induce a positive appearance and/or feelbenefit, but low enough to avoid serious side effects (i.e., to providea reasonable benefit to risk ratio, within the scope of sound judgmentof the ordinary skilled artisan). For example, an effective amount ofartichoke leaf extract and carob fruit extract herein means an amount ofthe two materials in combination that is sufficient to significantlyinduce a positive appearance and/or feel benefit, but low enough toavoid serious side effects (i.e., to provide a reasonable benefit torisk ratio, within the scope of sound judgment of the skilled artisan).

“Facial skin surface” means one or more of forehead, periorbital, cheek,perioral, chin, and nose skin surfaces.

“Skin care actives,” or “actives,” means compounds that, when applied tothe skin, provide a benefit or improvement to the skin.

“Improving the appearance of aging skin” or “improving the texture ofaging skin” means effecting a visually and/or tactilely perceptiblepositive change, or benefit, in skin texture appearance and/or feel.These terms also include preventing or delaying the appearance of one ormore textural signs of skin aging. Benefits that may be providedinclude, but are not limited to, one or more of the following: improvingthe appearance of wrinkles, fine lines, coarse deep lines, crevices,bumps; preventing loss of skin elasticity, for example, due to loss,damage and/or inactivation of functional skin elastin, resulting in suchconditions as elastosis, sagging, loss of skin recoil from deformation;and combinations thereof.

“Textural signs of skin aging” include but are not limited to, alloutward visibly and tactilely perceptible skin texture manifestations,as well as any macro- or microeffects, due to undesired changes in skintexture due to aging. These signs may result from processes whichinclude, but are not limited to, the development of texturaldiscontinuities such as wrinkles and coarse deep wrinkles, fine lines,skin lines, crevices, bumps, unevenness or roughness; loss of skinelasticity; keratoses; abnormal differentiation; hyperkeratinization;elastosis; collagen breakdown, and other histological changes in thestratum corneum, dermis, or epidermis; and combinations thereof.

I. Compositions

The present invention relates to various compositions and, morespecifically, to compositions for application to a skin surfaceincluding a wide variety of cosmetic compositions. The compositions maybe in various product forms that include, but are not limited to,solutions, suspensions, lotions, creams, gels, toners, sticks, pencil,sprays, aerosols, ointments, cleansing liquid washes and solid bars,shampoos and hair conditioners, pastes, foams, powders, mousses, shavingcreams, wipes, strips, patches, electrically-powered patches, wounddressing and adhesive bandages, hydrogels, film-forming products, facialand skin masks (with and without insoluble sheet), make-up such asfoundations, eye liners, and eye shadows, and the like. The compositionform may follow from the particular dermatologically acceptable carrierchosen, if present in the composition.

A. Artichoke Leaf and Carob Fruit Extracts

The compositions herein comprise an effective amount of artichoke leafextract and carob fruit extract in combination. As used herein, “incombination” means present in the same composition (e.g., as a blend),present in different compositions but applied contemporaneously (e.g.,close enough in time to result in the combined synergistic benefit ofthe two materials), or combinations thereof.

The amount of extract that is “effective” can differ from one particularsource (e.g., manufacturer) of extract to another, and can be determinedby the skilled artisan based upon the particular extract product's levelof activity (e.g., level of active components present). As with anyextract, the concentration of active components in the particularextract product to be used will depend on factors such as the finaldilution volume of the extract product, the particular extraction methodemployed, the natural range of variation among individual plants, andother common factors known to those skilled in the art.

The carob fruit extract (INCI name: Ceratonia siliqua fruit extract; CASNumber: 84961-45-5) of the present invention is made from the oblong,non-fleshy, bean-like pod that grows on the carob tree, which belongs tothe legume family Fabaceae. Carob is rich in oligogalactomannans, whichare believed to be important biological actives. The carob fruit podcontains large seeds commonly referred to as “carob nuts”.

Carob fruit extract suitable for use herein can be derived from thefruit pod, the seeds, or combinations thereof, using processes known inthe art. The carob fruit extract may include other suitable materialssuch as, for example, water, thickeners, humectants, solvents,solubilizers, etc. A suitable carob fruit extract for use herein iscommercially produced by Silab S.A. (France), under the trade nameGlyco-Repair™PX. This particular extract product contains approximately94% water, 5% carob fruit extract, and 1% other materials.

The carob fruit extract may be included in the composition herein at anamount of from 0.0001% to 15%, from 0.0002% to 10%, from 0.001% to 15%,from 0.025% to 10%, from 0.05% to 10%, from 0.05% to 5%, or even from0.1% to 5%, by weight of the total composition.

Artichoke leaf extract (INCI Name: Cynara scolymus extract; CAS number:84012-14-6) suitable for use herein may be derived from the long, deeplyserrated basal leaves of the artichoke plant. These leaves containhigher concentrations of biologically active compounds, such as caffeicacid derivatives (e.g., cynarin); flavonoids; and sesquiterpene lactones(e.g., cynaropicrin). It can be preferable to dry the leaves beforeextraction in order to achieve greater potency of certain activematerials. For example, cynarin is found only in trace amounts in thefresh leaves, but is formed by natural chemical changes that take placeduring drying and extraction of the plant material.

The artichoke leaf extract may include other suitable materials such as,for example, water, thickeners, humectants, solvents, solubilizers, etc.The artichoke leaf extract can be prepared by suitable processes knownin the art. An example of a commercially available artichoke leafextract suitable for use herein is Biobenefity™, made by IchimaruPharcos Corp. (Gifu, Japan).

In some embodiments, the composition may include artichoke leaf extractin an amount of from 0.0001% to 15%, from 0.0002% to 10%, from 0.001% to15%, from 0.025% to 10 from 0.05% to 10%, from 0.05% to 5%, or even from0.1% to 5%, by weight of the total composition.

B. Skin Tone Agent

In some embodiments, it may be desirable to include a skin tone agent inthe composition. The skin tone agents can be included to further improveoverall skin tone. When present, the compositions of the presentinvention contain up to about 50%, 40%, 30%, 20%, 10%, 5%, or 3%, byweight of the composition, of the skin tone agent. When present, thecompositions of the present invention contain at least about 0.001%,0.01%, 0.1%, 0.2%, 0.5%, or 1%, by weight of the composition, of theskin tone agent. Suitable ranges include any combination of the lowerand upper limits including suitable ranges from about 0.1% to about 50%;from about 0.2% to about 20%; or from about 1% to about 10%, by weightof the composition, of the skin tone agent. The amounts listed hereinare only to be used as a guide, as the optimum amount of the skin toneagent will depend on the specific active selected since their potencydoes vary considerably.

Suitable skin tone agents include, but are not limited to, sugar amines,vitamin B3 compounds, arbutin, deoxyarbutin,1,3-dihydroxy-4-alkylbenzene such as hexylresorcinol, sucrosedilaurante, bakuchoil (4[(1E, 3S)-3-ethenyl-3,7-dimethyl—1,6 octadienyl]phenol or monterpene phenol), pyrenoine (available from Biotech Marine,France), panicum miliaceum seed extract, arlatone dioic acid, cinnamicacid, ferulic acid, achromaxyl, methyl nicotinamide, oil solublelicorice extract, folic acid, undecylenic acid (i.e., undecenoic acid),zinc undecylenate, thiamine (Vitamin B1) and its hydrochloride,L-tryptophan, helianthus annuus (sunflower) and vitis vinifera (grape)leaf extract, carnosine (i.e., dragosine), methyl gentisate,1,2-hexandiol and 1,2-octandiol (i.e., combination sold as Symdiol 68 bySymrise AG, Germany), inositol, decylenoylphenylalanine (e.g., soldunder the tradename Sepiwhite by Seppic, France), kojic acid, hexamidinecompounds, salicylic acid, and retinoids including retinol and retinylpropionate.

In certain embodiments, the additional skin tone agent is selected fromvitamin B3 compounds, sugar amines, hexamidine compounds, salicylicacid, 1,3-dihydroxy-4-alkylbenzene such as hexylresorcinol, andretinoids. As used herein, “vitamin B₃ compound” means a compound havingthe formula:

wherein R is —CONH₂ (i.e., niacinamide), —COOH (i.e., nicotinic acid) or—CH₂OH (i.e., nicotinyl alcohol); derivatives thereof; and salts of anyof the foregoing. As used herein, “sugar amine” includes isomers andtautomers of such and its salts (e.g., HCl salt) and its derivatives.Examples of sugar amines include glucosamine, N-acetyl glucosamine,mannosamine, N-acetyl mannosamine, galactosamine, N-acetylgalactosamine, their isomers (e.g., stereoisomers), and their salts(e.g., HCl salt). As used herein, “hexaminide compound” means a compoundhaving the formula:

wherein R¹ and R² are optional or are organic acids (e.g., sulfonicacids, etc.). In one embodiment, hexamidine compound is hexamidinediisethionate.

C. Anti-Inflammatory Agents

The composition can additionally comprise anti-inflammatory agents,which can be useful for improving the appearance of hyperpigmentationresulting from skin inflammation. Transient inflammatory eventstriggering hyperpigmentation and, more specifically, post-inflammatoryhyperpigmentation include, but are not limited to, acne lesions, ingrownhairs, scratches, insect bites, surfactant damage, allergens, andshort-term UV exposure. Inflammation induced hyperpigmentation includingpost-inflammatory hyperpigmentation may be managed by incorporating intothe compositions of the present invention an anti-inflammatory agent.When present, the compositions of the present invention contain up toabout 20%, 10%, 5%, 3%, or 1% by weight of the composition, of theanti-inflammatory agent. When present, the compositions of the presentinvention contain at least about 0.001%, 0.01%, 0.1%, 0.2%, 0.3%, 0.5%,or 1%, by weight of the composition, of the anti-inflammatory agent.Suitable ranges include any combination of the lower and upper limits.Suitable anti-inflammatory agents include, but are not limited tononsteroidal anti-inflammatory agents (NSAIDS including but not limitedto ibuprofen, naproxen, flufenamic acid, etofenamate, aspirin, mefenamicacid, meclofenamic acid, piroxicam and felbinac), glycyrrhizic acid(also known as glycyrrhizin, glycyrrhixinic acid, and glycyrrhetinicacid glycoside) and salts such as dipotassium glycyrrhizate,glycyrrhetenic acid, licorice extracts, bisabolol (e.g., alphabisabolol), manjistha (extracted from plants in the genus Rubia,particularly Rubia cordifolia), and guggal (extracted from plants in thegenus Commiphora, particularly Commiphora mukul), kola extract,chamomile, red clover extract, and sea whip extract (extracts from plantin the order Gorgonacea), derivatives of any of the foregoing, andmixtures thereof.

D. Sunscreen Actives

The compositions of the subject invention may comprise one or moresunscreen actives (or sunscreen agents) and/or ultraviolet lightabsorbers. Herein, “sunscreen active” collectively includes, sunscreenactives, sunscreen agents, and/or ultraviolet light absorbers. Sunscreenactives include both sunscreen agents and physical sunblocks. Sunscreenactives may be organic or inorganic. Examples of suitable sunscreenactives are disclosed in Personal Care Product Council's InternationalCosmetic Ingredient Dictionary and Handbook, Thirteenth Edition, as“sunscreen agents.” Particularly suitable sunscreen actives are2-ethylhexyl-p-methoxycinnamate (commercially available as PARSOL™ MCX),4,4′-t-butyl methoxydibenzoyl-methane (commercially available as PARSOL™1789), 2-hydroxy-4-methoxybenzophenone, octyldimethyl-p-aminobenzoicacid, digalloyltrioleate, 2,2-dihydroxy-4-methoxybenzophenone,ethyl-4-(bis(hydroxypropyl))aminobenzoate,2-ethylhexyl-2-cyano-3,3-diphenylacrylate, 2-ethylhexyl-salicylate,glyceryl-p-aminobenzo ate, 3,3,5-tri-methylcyclohexylsalicylate, menthylanthranilate, p-dimethyl-aminobenzoic acid or aminobenzoate,2-ethylhexyl-p-dimethyl-amino-benzoate, 2-phenylbenzimidazole-5-sulfonicacid, 2-(p-dimethylaminophenyl)-5-sulfonicbenzoxazoic acid, octocrylene,zinc oxide, benzylidene camphor and derivatives thereof, titaniumdioxide, and mixtures thereof.

In one embodiment, the composition may comprise from about 1% to about20%, and alternatively from about 2% to about 10% by weight of thecomposition, of the sunscreen active. Exact amounts will vary dependingupon the chosen sunscreen active and the desired Sun Protection Factor(SPF), which is within the knowledge of one of skilled in the art.

E. Optional Components

The compositions of the present invention may contain a variety of otheringredients provided that they do not unacceptably alter the benefits ofthe invention. When present, compositions of the present invention maycontain from about 0.0001% to about 50%; from about 0.001% to about 20%;or, alternately, from about 0.01% to about 10%, by weight of thecomposition, of the optional components. The amounts listed herein areonly to be used as a guide, as the optimum amount of the optionalcomponents used in a composition will depend on the specific activeselected since their potency does vary considerably. Hence, the amountof some optional components useful in the present invention may beoutside the ranges listed herein.

The optional components, when incorporated into the composition, shouldbe suitable for use in contact with human skin tissue without unduetoxicity, incompatibility, instability, allergic response, and the like.The compositions of the present invention may include optionalcomponents such as anti-acne actives, desquamation actives,anti-cellulite agents, chelating agents, flavonoids, tanning active,non-vitamin antioxidants and radical scavengers, hair growth regulators,anti-wrinkle actives, anti-atrophy actives, minerals, phytosterolsand/or plant hormones, N-acyl amino acid compounds, antimicrobial orantifungal actives, and other useful skin care actives, which aredescribed in further detail in U.S. application publication No.US2006/0275237A1 and US2004/0175347A1.

The Personal Care Product Council's International Cosmetic IngredientDictionary and Handbook, Thirteenth Edition, describes a wide variety ofnon-limiting cosmetic and pharmaceutical ingredients commonly used inthe skin care industry, which are suitable optional components for usein the compositions of the present invention. Examples of theseingredient classes include: abrasives, absorbents, aesthetic componentssuch as fragrances, pigments, colorings/colorants, essential oils,anti-caking agents, antifoaming agents, antimicrobials, binders,biological additives, buffering agents, bulking agents, chelatingagents, chemical additives, colorants, cosmetic astringents, cosmeticbiocides, denaturants, drug astringents, emollients, externalanalgesics, film formers or materials, opacifying agents, pH adjusters,preservatives, propellants, reducing agents, sequestrants, skin coolingagents, skin protectants, thickeners viscosity modifiers, vitamins, andcombinations thereof.

F. Dermatologically Acceptable Carrier

The compositions of the present invention may also comprise adermatologically acceptable carrier (which may be referred to as“carrier”) for the composition. The phrase “dermatologically acceptablecarrier”, as used herein, means that the carrier is suitable for topicalapplication to the keratinous tissue, has good aesthetic properties, iscompatible with the actives in the composition, and will not cause anyunreasonable safety or toxicity concerns. In one embodiment, the carrieris present at a level of from about 50% to about 99%, about 60% to about98%, about 70% to about 98%, or, alternatively, from about 80% to about95%, by weight of the composition.

The carrier can be in a wide variety of forms. Non-limiting examplesinclude simple solutions (e.g., aqueous, organic solvent, or oil based),emulsions, and solid forms (e.g., gels, sticks, flowable solids, oramorphous materials). In certain embodiments, the dermatologicallyacceptable carrier is in the form of an emulsion. Emulsion may begenerally classified as having a continuous aqueous phase (e.g.,oil-in-water and water-in-oil-in-water) or a continuous oil phase (e.g.,water-in-oil and oil-in-water-in-oil). The oil phase of the presentinvention may comprise silicone oils, non-silicone oils such ashydrocarbon oils, esters, ethers, and the like, and mixtures thereof.

The aqueous phase typically comprises water. However, in otherembodiments, the aqueous phase may comprise components other than water,including but not limited to water-soluble moisturizing agents,conditioning agents, anti-microbials, humectants and/or otherwater-soluble skin care actives. In one embodiment, the non-watercomponent of the composition comprises a humectant such as glycerinand/or other polyols. However, it should be recognized that thecomposition may be substantially (i.e., less than 1% water) or fullyanhydrous.

A suitable carrier is selected to yield a desired product form.Furthermore, the solubility or dispersibility of the components (e.g.,extracts, sunscreen active, additional components) may dictate the formand character of the carrier. In one embodiment, an oil-in-water orwater-in-oil emulsion is preferred.

Emulsions may further comprise an emulsifier. The composition maycomprise any suitable percentage of emulsifier to sufficiently emulsifythe carrier. Suitable weight ranges include from about 0.1% to about 10%or about 0.2% to about 5% of an emulsifier, based on the weight of thecomposition. Emulsifiers may be nonionic, anionic or cationic. Suitableemulsifiers are disclosed in, for example, U.S. Pat. No. 3,755,560, U.S.Pat. No. 4,421,769, and McCutcheon's Detergents and Emulsifiers, NorthAmerican Edition, pages 317-324 (1986). Suitable emulsions may have awide range of viscosities, depending on the desired product form.

The carrier may further comprise a thickening agent as are well known inthe art to provide compositions having a suitable viscosity andrheological character.

II. Methods of Treatment

Various methods of treatment, application, regulation, or improvementmay utilize the aforementioned compositions. Identification of a regionof aging skin may occur on any skin surface of the body. Skin surfacesof the most concern tend to be those not typically covered by clothingsuch as facial skin surfaces, hand and arm skin surfaces, foot and legskin surfaces, and neck and chest skin surfaces (e.g., décolletage). Inparticular, identification of the region of aging skin may be on afacial skin surface including the forehead, perioral, chin, periorbital,nose, and/or cheek skin surfaces.

The method may comprise the step of applying the composition to thepreviously identified area of aging skin, or an area where one seeks toprevent the appearance of aging skin. Many regimens exist for theapplication of the composition. The composition may be applied at leastonce a day, twice a day, or on a more frequent daily basis, during atreatment period. When applied twice daily, the first and secondapplications are separated by at least 1 to about 12 hours. Typically,the composition may be applied in the morning and/or in the eveningbefore bed.

The treatment period is ideally of sufficient time to provide animprovement in the appearance of aging skin. The treatment period may beat least about 1 week, and in some embodiments the treatment period maylast about 4 weeks, 8 weeks, or 12 weeks. In certain embodiments, thetreatment period will extend over multiple months (i.e., 3-12 months) ormultiple years. In one embodiment the composition is applied at leastonce a day during a treatment period of at least about 4 weeks, 8 weeks,or 12 weeks. In one embodiment the composition is applied twice a dayduring a treatment period of at least about 4 weeks, 8 weeks, or 12weeks.

The step of applying the composition may be accomplished by localizedapplication. In reference to application of the composition, the terms“localized”, “local”, or “locally” mean that the composition isdelivered to the targeted area (e.g., wrinkles around the eyes) whileminimizing delivery to skin surface not requiring treatment. Thecomposition may be applied and lightly massaged into area of aging skin.The form of the composition or the dermatologically acceptable carriershould be selected to facilitate localized application. While certainembodiments of the present invention contemplate applying a compositionlocally to an area, it will be appreciated that compositions of thepresent invention can be applied more generally or broadly to one ormore skin surfaces.

In some embodiments, the composition may be delivered by a variety ofapplicators appropriate for localized and general application. Suchapplicators can include droppers, applicator wands, cotton swabs, or anyother suitable device. Other suitable applicators include SH-0127 penapplicator available from Shya Hsin Plastic Works, Inc., Taiwan andeither the Xpress Tip or liquid filled swab available from SwabPlus,Inc., China. The applicator may be configured to easily apply thecomposition to signs of aging, such as fine lines and wrinkles, andallowing for a dosed amount of the composition of between about 1 toabout 50 uL/cm² or between about 1 to about 5uL/cm². In anotherembodiment, the composition is applied to the one or more signs of agingand more generally to one or more facial skin surfaces contemporaneously(i.e., over a period of less than 30 minutes or, more typically, lessthan 5 minutes).

While some methods described herein contemplate applying thecompositions of the present invention with an applicator, it will beappreciated that applicators are not required and the compositions ofthe present invention can also be applied directly by using one's fingeror in other conventional manners.

In one embodiment, the method comprises the steps of applying a firstcomposition comprising an effective amount of artichoke leaf extract andcarob fruit extract to a skin surface and of applying a secondcomposition to the skin surface, before or after the first composition.The first and second compositions may be any compositions describedherein; however, the second composition may optionally comprise aneffective amount of the artichoke leaf extract and carob fruit extractblend present in the first composition. The second composition maycomprise one or more tone agents, sunscreen actives, anti-inflammatoryagents, or optional components. The first composition may be generallyor locally applied, while the second composition may be generally orlocally applied to the skin surface including the aging skin to whichthe first composition is applied. In certain embodiments, the skinsurface is facial skin surface which include one or more of theforehead, perioral, chin, periorbital, nose, and cheek skin surfaces. Inanother embodiment, the first and second compositions are appliedcontemporaneously to at least the cheek, forehead, and chin/perioralskin surfaces. For general application to a skin surface and,particularly a facial skin surface, the dosed amount of the first orsecond composition may be between about 1 to about 50 uL/cm² perapplication (i.e., per single application to the skin surfaces).

Suitable methods may comprise any one or more of the abovementionedsteps. All of the aforementioned steps are applicable to application,treatment, regulation, and/or improvement of aging skin appearance. Onesuitable method of improving the appearance of aging skin includes thestep of topically applying a composition comprising an effective amountof artichoke leaf extract and carob fruit extract blend to the agingskin surface, wherein the composition is applied for a period of timesufficient to improve the appearance of the aging skin.

III. Mechanisms of Action

With aging, the protective function of the skin's epidermal barrier maybecome impaired. For example, the aging epidermal barrier may sufferincreased permeability to harmful stimuli (e.g., free radicals), areduction in the amount of lipid in the intercellular matrix, and/or adecreased capacity to diffuse toxins from deeper layers, which can leadto harmful stimuli penetrating the stratum corneum more easily. As aresult, the underlying dermal layers may suffer increased damage suchas, for example, degradation of collagen and elastin, and thinning ofthe stratum corneum. Thus, the recovery capacity of the epidermalbarrier is substantially reduced, and the effects of aging may becomevisably evident by the appearance of, for example, fine lines, wrinkles,and/or other textural signs of skin aging.

A cluster of nine genes associated with epidermal barrier function andthe skin's ability to regenerate and protect itself from the texturalsigns of skin aging is set forth in Table 2 (Example 2) below, alongwith the associated epidermal function of each gene. These genes aredifferentially expressed by the epidermis. Down-regulation of thesegenes is associated with impaired epidermal barrier function and theresulting appearance of textural signs of skin aging. Conversely,up-regulation of these genes corresponds to an improved epidermalbarrier function, leading to improved textural appearance of the agingskin.

EXAMPLES Example 1 Exemplary Compositions

Table 1 sets forth non-limiting examples of the compositions of thepresent invention. The examples are given solely for the purpose ofillustration and are not to be construed as limitations of the presentinvention, as many variations thereof are possible without departingfrom the spirit and scope of the invention, which would be recognized byone of ordinary skill in the art. In the examples, all concentrationsare listed as weight percent, unless otherwise specified and may excludeminor materials such as diluents, filler, and so forth. The listedformulations, therefore, comprise the listed components and any minormaterials associated with such components. As is apparent to one ofordinary skill in the art, the selection of these minor materials willvary depending on the physical and chemical characteristics of theparticular ingredients selected to make the present invention asdescribed herein.

All examples may be used to treat or improve the appearance of one ormore signs of aging. The present invention may further relate to aregimen involving the localized treatment for one or more aging signs bya first composition (e.g., Examples A or B) and a more broad or generalfacial skin treatment by a second composition (e.g., Examples C or D),which can be applied before or after the localized treatment to improvea particular sign of aging (e.g., across the entire face).

TABLE 1 Exemplary Compositions Ex- Ex- Ex- Ex- am- am- am- am-Component/% by wt. ple A ple B ple C ple D Carob Fruit Extract (Glyco-0.55 1.00 0.55 0.00 Repair ™PX, available from Silab S.A.) ArtichokeLeaf Extract (Bio- 0.10 0.20 0.20 0.00 Benefity ™, available fromIchimaru Pharcos Corp.) N-Acetylglucosamine 0.00 0.00 2.00 0.00Hexamidine Diisethionate 0.00 0.00 0.09 0.09 Sepiwhite ™ (Undecylenoyl-0.00 0.00 0.50 0.50 phenylalanine, neutralized) (available from SEPPIC)Sepigel 305 ™ (Polyacrylamide + 0.00 0.00 2.00 2.00 C13-14 isoparaffin +laureth-7) (available from SEPPIC) Dipotassium Glycyrrhizate 0.00 0.100.10 0.30 Hexamidine Diisethionate 0.00 0.00 0.09 0.09 Homosalate 0.000.00 0.00 9.00 Avobenzone 0.00 0.00 0.00 3.00 Octocrylene 0.00 0.00 0.002.60 Oxybenzone 0.00 0.00 0.00 1.00 Octisalate 0.00 0.00 0.00 4.50Butylene Glycol (CAS No. 5.50 5.50 5.50 5.50 107-88-0) Niacinamide (CASNo. 98-92-0) 5.00 5.00 5.00 5.00 Glycerin (CAS No. 56-81-5) 2.50 2.502.50 2.50 DC 1503 Fluid ™ (available from 2.50 2.50 2.50 2.50DowCorning) Lubrajel Oil ™ (available from 1.44 1.44 1.44 1.44 Sederma)Phenonip XB ™ (available from 1.25 1.25 1.25 1.25 Clariant) D-panthenol(CAS No. 81-13-0) 1.00 1.00 1.00 1.00 Tospearl 2000 ™ (Polymethylsils1.00 1.00 1.00 1.00 esquioxane) (CAS No. 68554-70-1) (available from GESilicones/Momentive) DL-Alpha Tocopheryl Acetate 0.50 0.50 0.50 0.50(CAS No. 7695-91-2) Prodew 400 ™ (available from 0.50 0.50 0.50 0.50Ajinomoto) Pemulen TR-2 ™ (Acrylates/ 0.25 0.25 0.25 0.25 C10-30 AlkylAcrylate Crosspolymer) (available from Noveon) Polysorbate 20 (CAS No.0.25 0.25 0.25 0.25 9005-64-5) Sodium Metabisulfite (CAS No. 0.25 0.250.25 0.25 7681-57-4) Allantoin (CAS No. 97-59-6) 0.20 0.20 0.20 0.20Sodium Hydroxide (CAS No. 0.17 0.17 0.17 0.17 1310-73-2) (50% solutionby weight in water) Disodium EDTA (CAS No. 0.10 0.10 0.10 0.10 139-33-3)Xanthan Gum (CAS No. 0.05 0.05 0.05 0.05 11138-66-2) Sodium Hyaluronate(CAS No. 0.01 0.01 0.01 0.01 9067-32-7) Water (CAS No. 7732-18-5) QS QSQS QS TOTAL (% by weight of total 100.00 100.00 100.00 100.00composition)

The compositions herein are generally prepared by conventional methodssuch as are known in the art of making topical compositions. Suchmethods typically involve mixing of the ingredients in one or more stepsto a relatively uniform state, with or without heating, cooling,application of vacuum, and the like. Typically, emulsions are preparedby first mixing the aqueous phase materials separately from the fattyphase materials and then combining the two phases as appropriate toyield the desired continuous phase. The compositions may be prepared tooptimize stability (physical stability, chemical stability,photostability) and/or delivery of the active materials. Thisoptimization may include appropriate pH (e.g., less than 7), exclusionof materials that can complex with the active agent and thus negativelyimpact stability or delivery (e.g., exclusion of contaminating iron),use of approaches to prevent complex formation (e.g., appropriatedispersing agents or dual compartment packaging), use of appropriatephotostability approaches (e.g., incorporation of sunscreen/sunblock,use of opaque packaging), etc.

Example 2 Ex Vivo Tissue Analysis

In this Example, the effect of an artichoke-carob blend on a cluster ofnine genes associated with epidermal barrier function and the skin'sability to regenerate and protect itself from the textural signs of skinaging was evaluated. These genes are set forth in Table 2, along withthe associated epidermal function of each gene. The genes shown in Table2 are differentially expressed by the epidermis. For example,down-regulation of these genes is associated with impaired epidermalbarrier function and the resulting appearance of textural signs of skinaging. Conversely, up-regulation of these of these genes corresponds toan improved epidermal barrier function, leading to improved texturalappearance of the aging skin.

TABLE 2 Representative Epidermal-Associated Genes Having DecreasedExpression with Skin Aging Gene Associated Function Keratin 2Synthesized during maturation of epidermal keratinocytes (KRT2) andlocalized in the upper-intermediate spinous layer of the epidermisKeratin 6A Keratin associated with proliferating epidermis (KRT6A)Claudin-1 An integral membrane protein and a component of the (CLDN1)tight junction; associated with barrier function Loricrin Major proteincomponent of the cornified cell envelope (LOR) found in terminallydifferentiated epidermal cells Filaggrin Aggregates keratin intermediatefilaments and promotes (FLG) disulfide-bond formation among theintermediate filaments during terminal differentiation of mammalianepidermis; associated with barrier function Involucrin Component of thekeratinocyte crosslinked envelope; (IVL) synthesised in the stratumspinosum and cross-linked in the stratum granulosum by thetransglutaminase enzyme that makes it highly stable; associated withbarrier function Keratin 10 Associated with differentiated epidermis(KRT10) Aquaporin 3 A water channel expressed in keratinocytesassociated (AQP3) with moisture benefits Keratin, type Epidermalintermediate filament I cytoskeletal 14 (KRT14)

Ex Vivo Tissue Method.

Skin explants were collected from surgical waste, cultured on transwellinserts, and treated with actives in media. Control skin was untreated.After 7 days, punch biopsies were taken for RNA isolation and PCRanalysis.

RT-PCR Method.

Purified RNA is converted to cDNA using Quanta iScript™, 500 ng of RNAis mixed with iScript and run on a thermocycler according to kitinstructions. One ul of the resulting cDNA is then mixed with QuantaPerfecta Master™ mix according to instructions and aliquoted acrossSAbiosciences™ custom array plate. The plate is then sealed and run onthe Step-one Plus ™ machine from Applied Biosystems™. The data analysisis performed by uploading raw data into the data analysis software fromSAbiosciences™.

Individual artichoke leaf and carob fruit extracts, as well as theircombination, were evaluated according to the Ex Vivo tissue Method andRT-PCR Method described herein. The fold-increase/decrease inexpression, versus control, was measured for the artichoke leaf extractand carob fruit extract separately and in combination. As shown in Table3, the blend effected a positive fold increase in all nine genes (fourstatistically significant, five trending), indicating the desirableup-regulation of those genes, and thus a positive textural anti-agingbenefit. The results illustrated in Table 3 demonstrate that thecombination of artichoke leaf extract with carob fruit extract producesa synergistic increase in the up-regulation of theseepidermal-associated genes. For each of the nine genes, as shown byTable 3, the artichoke-carob blend exhibited an up-regulated foldincrease that exceeded the expected additive effect of the artichokeleaf and carob fruit extracts separately.

TABLE 3 Synergistic Effect of Artichoke Leaf Extract + Carob FruitExtract Artichoke Carob Blend of Artichoke Expected Leaf Fruit LeafExtract Additive Extract Extract 0.03% + Carob Effect of 0.03% 0.005%Fruit Extract Combination Gene [A] [B] 0.005% [C] [Sum of A + B] *KRT21.50 −1.35 1.72* 0.15 KRT6A −1.05 −1.34 1.26 −2.39 CLDN1 −1.03 −1.3 1.07−2.33 LOR 1.49 −1.07 1.33 0.42 *FLG 1.58 −1.26 1.76* 0.32 IVL −1.06−1.68 1.06 −2.74 **KRT10 −1.1 −1.78 1.79** −2.88 AQP3 1.04 −1.46 1.26−0.42 *KRT14 1.11 −1.13 1.34* −0.02 *Statistically significant p < 0.1**Statistically significant p < 0.05

Example 3 Method of Treatment

A test subject topically applies a composition comprising 0.03%artichoke leaf extract+0.005% carob fruit extract, by weight in avehicle, to the entire face one to two times a day for 12 weeks. Thesubject's facial skin is evaluated at week 4, week 8, and week 12 oftreatment. At each evaluation, the subject's facial skin feels andappears to be more hydrated, and the subject notices a decrease in theappearance of fine lines and wrinkles.

The dimensions and values disclosed herein are not to be understood asbeing strictly limited to the exact numerical values recited. Instead,unless otherwise specified, each such dimension is intended to mean boththe recited value and a functionally equivalent range surrounding thatvalue. For example, a dimension disclosed as “40 mm” is intended to mean“about 40 mm.”

Every document cited herein, including any cross referenced or relatedpatent or application, is hereby incorporated herein by reference in itsentirety unless expressly excluded or otherwise limited. The citation ofany document is not an admission that it is prior art with respect toany invention disclosed or claimed herein or that it alone, or in anycombination with any other reference or references, teaches, suggests ordiscloses any such invention. Further, to the extent that any meaning ordefinition of a term in this document conflicts with any meaning ordefinition of the same term in a document incorporated by reference, themeaning or definition assigned to that term in this document shallgovern.

While particular embodiments of the present invention have beenillustrated and described, it would be obvious to those skilled in theart that various other changes and modifications can be made withoutdeparting from the spirit and scope of the invention. It is thereforeintended to cover in the appended claims all such changes andmodifications that are within the scope of this invention.

What is claimed is:
 1. A stable skin care composition for improving theappearance of aging skin, the stable skin care composition comprising:a. about 0.001% to about 5% of an artichoke leaf extract; b. about0.001% to about 5% of a carob fruit extract, wherein the carob fruitextract comprises an oligogalactomannan; c. a dermatologicallyacceptable carrier; d. a pH of less than 7; e. wherein the compositionis substantially free of materials that complex with the artichoke leafextract and the carob fruit extract; and f. wherein the artichoke leafextract and the carob fruit extract are present at an amount to providea synergistic increase in the up-regulation of at least oneepidermal-associated gene selected from the group consisting of KRT2,KRT6A, CLDN1, LOR, FLG, IVL, KRT10, AQP3, and KRT14 according to an exvivo tissue analysis.
 2. The skin care composition of claim 1, whereinthe epidermal-associated gene is selected from the group consisting ofKRT2, FLG, KRT10, and KRT14.
 3. The skin care composition of claim 1,wherein the composition further comprises at least one additional skinactive selected from the group consisting of sunscreen actives,anti-inflammatory agents, and skin tone actives.
 4. The skin carecomposition of claim 3, wherein the additional skin active is asunscreen active, and the sunscreen active is selected to helpphotostablize the skin care composition.
 5. The skin care composition ofclaim 3, wherein the composition is formulated to prevent the formationof a chemical complex with the additional skin care active.
 6. The skincare composition of claim 1, wherein at least a portion of the artichokeleaf extract is obtained from basal leaves of an artichoke plant.
 7. Theskin care composition of claim 1, wherein the artichoke leaf extract isobtained from dried artichoke leaves.
 8. The skin care composition ofclaim 1, further comprising an emulsion having an aqueous continuousphase, wherein the artichoke leaf extract and carob fruit extract aredisposed in the aqueous continuous phase of the emulsion.
 9. A skin careproduct, comprising: a. the skin care composition of claim 1; and b. anopaque package, wherein the skin care composition is disposed in theopaque package, and the opaque package helps photostablize the skin carecomposition.
 10. The skin care product of claim 9, further comprising anapplicator.